Aside from providing buoyancy and protection for brain, the functional significance of cerebrospinal fluid (CSF) remains poorly understood. The objective of this study is to evaluate the hypothesis that CSF functions as an excretory system for brain by following the time course and route of removal from rat brain of test substances injected into identified intracerebral sites. Test compounds would include radioisotopes, to follow material transport quantitatively, and horseradish peroxidase, to define anatomical pathways of exchange. Results would relate to the relative importance of CSF and of cerebral capillaries as routes of material excretion from brain, to mechanisms of molecular transport from brain to CSF (bulk flow or diffusion), and to the possible role of perivascular spaces as preferential channels of fluid exchange between brain and CSF. Mathematical models predicting rates and routes of removal from brain would be developed and control studies would assess the effects of intracerebral cannula implantation and fluid injection on the results. Methods developed for studying interstitial fluid physiology in rat brain would be adapted to central and peripheral nerves with the aim of developing a simpler model system for studying the production, circulation and reabsorption of cerebral interstitial fluid.